Digital enzyme linked immunosorbent assay (ELISA) is an ultra-sensitive technology for detecting biomarkers and
viruses etc. As a conventional ELISA technique, a target molecule is bonded to an antibody with an enzyme by antigen-antibody reaction. In this technology, a femto-liter droplet chamber array is used as reaction chambers. Due to its small
volume, the concentration of fluorescent product by single enzyme can be sufficient for detection by a fluorescent
microscopy. In this work, we demonstrate a miniaturized lensless imaging device for digital ELISA by using a custom
image sensor. The pixel array of the sensor is coated with a 20 μm-thick yellow filter to eliminate excitation light at 470
nm and covered by a fiber optic plate (FOP) to protect the sensor without resolution degradation. The droplet chamber
array formed on a 50μm-thick glass plate is directly placed on the FOP. In the digital ELISA, microbeads coated with
antibody are loaded into the droplet chamber array, and the ratio of the fluorescent to the non-fluorescent chambers with
the microbeads are observed. In the fluorescence imaging, the spatial resolution is degraded by the spreading through the
glass plate because the fluorescence is irradiated omnidirectionally. This degradation is compensated by image
processing and the resolution of ~35 μm was achieved. In the bright field imaging, the projected images of the beads
with collimated illumination are observed. By varying the incident angle and image composition, microbeads were
The structures in advanced complementary metal-oxide-semiconductor (CMOS) integrated circuit technology are in the range of deep-submicron. It allows designing and integrating nano-photonic structures for the visible to near infrared region on a chip. In this work, we designed and fabricated an image sensor with on-pixel metal wire grid polarizers by using a 65-nm standard CMOS technology. It is known that the extinction ratio of a metal wire grid polarizer is increased with decrease in the grid pitch. With the metal wire layers of the 65-nm technology, the grid pitch sufficiently smaller than the wavelengths of visible light can be realized. The extinction ratio of approximately 20 dB has been successfully achieved at a wavelength of 750 nm. In the CMOS technologies, it is usual to include multiple metal layers. This feature is also useful to increase the extinction ratio of polarizers. We designed dual layer polarizers. Each layer partially reflects incident light. Thus, the layers form a cavity and its transmission spectrum depends on the layer position. The extinction ratio of 19.2 dB at 780 nm was achieved with the grid pitch greater than the single layer polarizer. The high extinction ratio is obtained only red to near infrared region because the fine metal layers of deepsubmicron standard CMOS process is usually composed of Cu. Thus, it should be applied for measurement or observation where wide spectrum is not required such as optical rotation measurement of optically active materials or electro-optic imaging of RF/THz wave.
Green fluorescent materials such as Green Fluorescence Protein (GFP) and fluorescein are often used for observing
neural activities. Thus, it is important to observe the fluorescence in a freely moving state in order to understand neural
activities corresponding to behaviors. In this work, we developed an implantable CMOS imaging device for in-vivo
green fluorescence imaging with efficient excitation light rejection using a combination of absorption filters. An
interference filter is usually used for a fluorescence microscope in order to achieve high fluorescence imaging sensitivity.
However, in the case of the implantable device, interference filters are not suitable because their transmission spectra
depend on incident angle. To solve this problem we used two kinds of absorption filters that do not have angle
dependence. An absorption filter consisting of yellow dye (VARYFAST YELLOW 3150) was coated on the pixel array
of an image sensor. The rejection ratio of ideal excitation light (490 nm) against green fluorescence (510 nm) was
99.66%. However, the blue LED as an excitation light source has a broad emission spectrum and its intensity at 510 nm
is 2.2 x 10-2 times the emission peak intensity. By coating LEDs with the emission absorption filters, the intensity of the
unwanted component of the excitation light was reduced to 1.4 x 10-4. Using the combination of absorption filters, we achieved excitation light transmittance of 10-5 onto the image sensor. It is expected that high-sensitivity green
fluorescence imaging of neural activities in a freely moving mouse will be possible by using this technology.
The oscillation wavelength of a Nd3+-doped tellurite glass microsphere laser is controlled using a λΑ/4-shifted grating fabricated on the surface of the microsphere. The lasing wavelength is in agreement with the high transmission wavelength of the grating estimated from the grating period and the effective index of the whispering gallery mode.
The authors have successfully demonstrated continuous-wave oscillation in a Nd-doped tellurite glass microsphere laser at 1.06 μm for the first time. Microspheres with diameters of 50 to a few hundred micrometres are fabricated by melting using an electric heater. Emission spectra reveal that the devices exhibit resonances corresponding to whispering gallery modes. Lasing threshold of pump power was about 5 mW.